The MOUNTAINEER‑03 clinical research study is evaluating if a study drug combination works compared to standard therapy for HER2‑positive, normal RAS cancer of the colon or rectum that is locally advanced, unresectable, or metastatic. Metastatic means the cancer has spread to other parts of the body, such as the lung or brain. Unresectable means the cancer cannot be removed by surgery. Locally advanced means the cancer has grown outside of the body part where it started but has not yet spread to other parts of the body.¹

To participate, a person cannot have previously received any treatment for metastatic colorectal cancer. However, it is permitted to receive a maximum of 2 doses of mFOLFOX6 in the metastatic setting before enrolling in the study. Participants may have received treatment for earlier stage colorectal cancer.

This clinical research study will aim to find out how the investigational study drug combination works compared to the current standard of care for those living with normal RAS, HER2‑positive metastatic colorectal cancer. This study will also test which side effects happen when participants take this combination of drugs.

This study is being done to test if tucatinib, trastuzumab, and mFOLFOX6 work to treat cancer of the colon or rectum that is normal RAS and HER2-positive. This combination of drugs is investigational, and it is being compared to the standard treatment with mFOLFOX6 alone or with either bevacizumab or cetuximab.

Tucatinib is a drug that is designed to target and turn off HER2.² People who are HER2-positive have cells that make extra amounts of HER2, which can lead to cancer.³ Turning off HER2 in cancer cells may make the cancer cells die or slow down their growth.³

In this study, tucatinib is used with trastuzumab. Trastuzumab is an antibody that is designed to attach to HER2.⁴ Antibodies are part of the immune system and usually help protect from getting sick. By attaching to HER2, trastuzumab may slow down or stop tumor cell growth.⁴

People who qualify and decide to participate in the clinical research study will help advance medical knowledge about normal RAS, HER2‑positive metastatic colorectal cancer.

While the clinical research study is ongoing, a team of study doctors and nurses at the study site will closely monitor participants’ health. A study team member is available to answer questions or concerns at any point throughout the clinical research study.

There are also risks involved in the MOUNTAINEER‑03 Study, including possible side effects from study treatment. This study drug combination may have little, if any, benefit to participants. Your cancer prognosis may or may not improve by taking part in the MOUNTAINEER‑03 Study.

Participation is voluntary, and participants are free to withdraw at any time, for any reason. The study doctor may discuss options for follow-up even if a participant is no longer receiving the investigational study drug. This follow-up is important because it helps us to understand how the investigational study drug works over time.

You will be tested for 2 types of genetic mutations—HER2 and RAS—to determine whether you are eligible to participate in the MOUNTAINEER-03 Study.

Human epidermal growth factor receptor 2 (HER2) is a protein. HER2 proteins are receptors on cells. A normal amount of HER2 is healthy—it helps to control how cells grow, divide, and repair themselves. However, having high levels of HER2 can cause the cell to grow out of control.³

If you have colorectal cancer, your doctor may test the levels of HER2 to find out if you're “positive” or “negative.” HER2+ (or HER2-positive) means that the cancer cells contain extra amounts of HER2.³

Approximately 3% to 5% of colorectal cancer tumors have too many copies of the HER2 gene and HER2 receptor. Your HER2 status may help your doctor choose a treatment for your colorectal cancer.³

Your doctor may also test for mutations in a group of genes called rat sarcoma viral oncogene homolog (RAS) genes. Mutations in RAS genes can cause cancer cells to grow and spread.⁵

The results of testing may show⁵:

• A normal RAS gene, also known as RAS wild-type (RAS WT)
• An abnormal RAS gene, also known as a mutated RAS gene

Determining your RAS status can help your doctor choose an appropriate treatment for your colorectal cancer.